This is a request for a high resolution electron microscope with energy dispersive x-ray microanalysis to support coordinated, ultrastructural investigations of the inner ear. The focus will be on the cochlear membranous labyrinth, with specific attention given to understanding of the causes of hearing impairment and the application of cochlear prosthesis. This instrumentation package will complement the research facilities of the Department of Otorhinolaryngology and KHRI and will create a unique center for ultrastructural investigations into cochlear pathology and the clinical use of cochlear prosthesis. Morphological analysis is a point of convergence of analytical and experimental studies taking an anatomical, behavioral, biochemical, electrophysiological approach to illuminate mechanisms underlying sensorineural hearing loss and the role of cochlear prosthesis in aiding hearing impaired individuals. The use of human and animal tissue in parallel should lead to a determination of the usefulness of animal models now employed for studies of hearing function. The need for a high resolution electron microscope is based upon the following specific aims of active and pending NIH grant support: 1) Examine ultrastructural features of the inner ear tissues after exposures to ototoxic agents (diuretics, antibiotics, antineoplastic agents) and to intense noise. 2) Detect heavy metals, e.g., antineoplastic agents (cis-platinum) distribution within inner ear cells. 3) Study the structural integrity of tight junctions of inner ear barriers when stressed by noise, ototoxic agents, and inner ear disease. 4) Examine the inner ear vasculature after administration of ototoxic drugs, noise, and in altered microhomeostatic conditions. 5) Identify viral particles in human inner ear specimens. 6) Examine ultrastructural effects of viral-induced cochlear and vestibular pathology. 7) Examine ultrastructural morphology of cultured epithelial and endothelial inner ear cells. 8) Measure electrolytes in cultured epithelial and endothelial cells of the inner ear. 9) Examine ultrastructural effects of prosthetic electrodes placed in the cochlea. 10) Detect mental dispersion of prosthetic electrodes within the cochlear tissues.